Inhibitory insula-ACC projections modulate affective but not sensory aspects of neuropathic pain.

Mol Brain

Department of Clinical Neurosciences, Alberta Children's Hospital Research Institute and Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.

Published: August 2023

The insula and anterior cingulate cortex (ACC) are brain regions that undergo structural and functional reorganization in neuropathic pain states. Here, we aimed to study inhibitory parvalbumin positive (PV+) posterior insula (pIC) to posterior ACC (pACC) projections, and to evaluate the effects of direct optogenetic manipulation of such projections on mechanical nociception and spontaneous ongoing pain in mice with Spared Nerve Injury (SNI). CTB tract-tracing in male PVCrexAi9 mice revealed a small proportion of PV+ projections from the pIC to the pACC. Electrophysiological analysis confirmed the existence of synaptic inputs into the pACC by pIC GABAergic cells. Optogenetic stimulation of these pathways did not change mechanical nociception, but induced conditioned place preference behavior responses. Our results suggest the presence of inhibitory projections between the pIC and the pACC which are able to selectively modulate affective aspects of neuropathic pain.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10440912PMC
http://dx.doi.org/10.1186/s13041-023-01052-8DOI Listing

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